Venous Thromboembolism:

1
Venous Thromboembolism Risk Assessment and
Prophylaxis
2

• VTE Prophylaxis
• Venous thromboembolism (VTE) is a leading cause
  of maternal mortality and severe morbidity
• Maternal death from VTE is amenable to prevention
• Prophylaxis is the most readily implementable
  means of systematically reducing the maternal
  death rate
• Protocols in the UK has led to significant
  reduction in maternal death from VTE
• Strategies for preventing VTE require minimal
  resources and are easily implementable

3

• Key Elements in VTE Prophylaxis Bundles
• Risk assessment tools  
• Protocols for antenatal and postpartum
  prophylaxis 
• Suggested dosing schedule
• Anesthesia recommendations
• Key references
• International Guidelines
• Key papers

4

• Risk Assessment
• All patients should be assessed for VTE risk
  multiple times in pregnancy including during
• Presentation for prenatal care
• Hospitalization for an antepartum indication
• Delivery hospitalization (in-house postpartum)
• Discharge from a delivery hospitalization
• Prophylaxis can be based on risk factors or can
  be empiric

5

• Risk Assessment
• Thromboembolism prophylaxis is a Joint Commission
  quality measures
• The Joint Commission states that all patients
  should receive VTE prophylaxis OR have
  documentation why no VTE prophylaxis was given
• Within a day of hospital admission
• Within a day of surgery
• The 2013 Joint Commission Specifications Manual
  for National Hospital Inpatient Safety

6
Risk Assessment Tools
7

• Risk Assessment Tools
• Sources
• Risk assessment tools were based on
  recommendations from major society guidelines
• Prenatal outpatient and postpartum discharge
  thromboprophylaxis are based primarily on
  American College of Chest Physicans and ACOG
  recommendations
• Inpatient prophylaxis is based primarily on RCOG
  recommendations
• Pharmacologic prophylaxis may be with
  unfractionated heparin (UFH) or low-molecular
  weight heparin (LMWH)
• Chest, Feb 2012 141
• ACOG Practice Bulletin No 123, 2011

8
Initial Assessment During Pregnancy
Clinical history
Anticoagulation
Multiple VTE episodes VTE with high-risk (HR)
thrombophilia VTE with acquired thrombophilia
Treatment dose LMWH or UFH
Idiopathic VTE VTE with pregnancy or oral
contraceptive VTE with low risk (LR)
thrombophilia Family history of VTE with HR
thrombophilia HR thrombophilia
Prophylactic LMWH or UFH

1st VTE provoked Family history of VTE with
LR thrombophilia LR thrombophilia (including
acquired)
No treatment
Chest, Feb 2012 141, ACOG Practice Bulletin
No 123, 2011
9
Risk Assessment
High-risk thrombophilia
Factor V Leiden or prothrombin gene mutation
homozygous Antithrombin III deficiency Compound
heterozygote disorders (FVL and prothrombin)
Low-risk thrombophilia
Factor V Leiden or prothrombin gene mutation
heterozygous Protein C or S deficiency
Acquired thrombophilia
Antiphospholipid antibody syndrome
ACOG Practice Bulletin No 123, 2011
10
Prevalence and Risks of VTE with Thrombophilias
Prev in Gen Pop Lifetime ? VTE Risk of all VTE VTE Risk/Preg (No hx) VTE Risk/Preg (Prior VTE)
Low-risk thrombophilias Low-risk thrombophilias Low-risk thrombophilias Low-risk thrombophilias Low-risk thrombophilias Low-risk thrombophilias
FVL heterozygote 1-15 3-8 40 lt 0.3 10
PTG heterozygote 2-5 3 17 lt 0.5 gt10
Protein C activity (lt50) 0.2-0.4 10-15 14 0.1-0.8 4-17
Protein S free Ag (lt55) .03-0.1 2 3 0.1 0-22
High-risk thrombophilias High-risk thrombophilias High-risk thrombophilias High-risk thrombophilias High-risk thrombophilias High-risk thrombophilias
FVL homozygote lt 1 2 1.5 17
PTG homozygote lt 1 0.5 2.8 gt 17
FVL/PTG compound 0.01 1-3 4.7 gt 20
Antithrombin III def (lt60) 0.02 25-50 1 3-7 40
Should not be tested in pregnancy or
high-estrogen states. If necessary, levels lt 24
in pregnancy in 1 series Paidas MJ, et al. J
Thromb Haemost 2005.
11
Initial Assessment During Pregnancy
Clinical history
Anticoagulation
Multiple VTE episodes VTE with high-risk (HR)
thrombophilia VTE with acquired thrombophilia
Treatment dose LMWH or UFH
Idiopathic VTE VTE with pregnancy or oral
contraceptive VTE with low risk (LR)
thrombophilia Family history of VTE with HR
thrombophilia HR thrombophilia (including
acquired)
Prophylactic LMWH or UFH
1st VTE provoked Family history of VTE with
LR thrombophilia LR thrombophilia
No treatment
Chest, Feb 2012 141, ACOG Practice Bulletin No
123, 2011
12

• Initial Assessment During Pregnancy
• Provoked VTE is defined as an event occurring in
  the setting of a temporary risk factor that
  increases risk such as
• Orthopedic surgery
• Indwelling line
• Immobilization
• Unprovoked VTE occurs in the absence of temporary
  risk factors.
• AN EXCEPTION VTE provoked by estrogen (OCP,
  prior pregnancy) should be treated as being at
  higher risk for recurrence and guidelines for
  unprovoked VTE should be followed for patients
  with this clinical history

13
Antepartum Hospitalization
All patients
Mechanical prophylaxis
AND
All patients
Should be given pharmacologic prophylaxis if
risk factors are present (next slide) OR May be
given pharmacologic prophylaxis empirically
14
Antepartum Hospitalization Risk-Factor Based
Prophylaxis
Recommend heparin if at least 1 of the factors
below is present
Medical conditions
Heart disease Lupus Renal disease Sickle
cell Major infection Other major medical
conditions
Already receiving LMWH or UFH as
outpatient Pre-pregnancy Morbid Obesity
(BMI gt 40) Any history of VTE
Prophylactic LMWH or UFH
OR 2 or more risk factors below are present

Pregnancy complications
Agegt40 or lt15 years Pre-pregnancy obesity (BMI
gt 30) Bed rest Any thrombophilia Medical
conditions Pregnancy complications
IUGR Preeclampsia Multiple gestation ART
RCOG, 2009 Green Top 37a
15
Delivery Hospitalization
Early mobilization Avoid dehydration Chemoprophyla
xis based on risk factors
All patients

• Women undergoing cesarean delivery should
• Receive sequential compression devices
  perioperatively and postpartum
• Receive chemoprophylaxis (LMWH or UFH) either
  empirically OR based on risk factors

16
Delivery Hospitalization
Recommend heparin if at least 1 of the factors
below is present
Already receiving heparin as outpatient
Pre-pregnancy class 3 obesity (BMI gt 40) Any
history of VTE Thrombophilia and family history
of VTE
OR 2 or more risk factors below are present
Prophylactic LMWH or UFH until discharge
2 or more risk factors Cesarean delivery
Hemorrhage Hysterectomy General
anesthesia Postpartum infection Agegt40
or lt15 years Pre-pregnancy obesity (BMI gt
30) Bed rest Any Thrombophilia
Medical or pregnancy complications

RCOG, 2009 Green Top 37a
17
Assessment During Postpartum Discharge
Clinical history
Anticoagulation
6 Weeks Treatment LMWH/UFH
Multiple VTE episodes VTE with high-risk (HR)
thrombophilia VTE with acquired thrombophilia

Idiopathic VTE VTE with pregnancy or oral
contraceptive VTE with low risk (LR)
thrombophilia Family history of VTE with HR
thrombophilia HR thrombophilia (including
acquired) VTE provoked LR thrombophilia and
family history of VTE
6 Weeks Prophylactic LMWH/UFH

(two changes from initial assessment)
No treatment
LR thrombophilia
Chest, Feb 2012 141 ACOG Practice Bulletin No
123, 2011
18

• Anticoagulation - LMWH
• Advantages of LMWH compared to UFH
• Fewer bleeding episodes
• Lower risk of heparin induced thrombocytopenia
  (HIT)
• Lower incidence of osteoporosis
• More predictable pharmacokinetics
• Anti-Xa activity measurement not required for
  LMWH except for
• Extremes of body weight
• Renal impairment
• LMWH has longer half life than UFH
• May be an advantage or a disadvantage

Greer et al. Blood. 2005106(2)401407 Ni Ainle
F et al. Blood Coagul Fibrinolysis. 200819
(7)689692 Nelson-Piercy C et al, Eur J Obstet
Gynecol Reprod Biol. 2011, Dec159(2)293-9.
19

• Contraindications to LMWH Therapy
• Hemophilia or other known bleeding disorder
• Active or threatened antenatal bleeding (e.g.
  placenta previa, placental abruption) based on
  clinical judgment of balancing risks/benefits
• Thrombocytopenia (platelet count lt75 x109)
• Recent stroke (hemorrhagic/ischemic)
• Severe renal disease (GFR lt30ml/min)
• Severe liver disease (prolonged PT)
• Uncontrolled hypertension (BP gt200mmHg systolic
  or gt120mmHg diastolic)
• Unfractionated heparin should be used if there
  is a specific contraindication to LMWH

20

• Screening for Heparin Induced Thrombocytopenia
  (HIT)
• For patients expected to be on either UFH or LMWH
  for greater than gt7 days a complete blood count
  should be sent to assess for HIT 7-10 days after
  initiation of therapy
• A platelet count of lt150,000/microL or acute drop
  tolt50 of baseline require further evaluation and
  immediate consultation with a hematologist or
  maternal-fetal medicine specialist
• A preceding diagnosis of gestational
  thrombocytopenia or idiopathic thrombocytopenic
  purpura may confound screening for HIT, and
  consultation with a hematologist or maternal
  fetal medicine specialist may be required for
  patients with these conditions

21

• Prophylaxis and Spontaneous Labor
• For patients on LMWH prenatally, consideration
  should be made to switch to UFH at 35-36 weeks
  gestational age to facilitate administration of
  regional anesthesia
• When patients are transitioned from LMWH to UFH,
  HIT should also be screened for with a CBC 7-10
  after UFH is initiated

22
Protocols for Prophylaxis
Protocols for Prophylaxis
Agent LMWH Enoxaparin   Dalteparin   Tinzaparin UFH Unfractionated heparin UFH Unfractionated heparin
Weight based Weight based Weight based Weight based Gestational age-based Gestational age-based
lt50kg 20mg daily 2500 units daily 3500 units daily First trimester 5000-7500 units Twice daily
50-90kg 40mg daily 5000 units daily 4500 units daily Second trimester 7500-10000 units Twice daily
91-130kg 60mg daily 7500 units daily 7000 units daily Third trimester   10000 units Twice daily
131-170kg 80mg daily 10000 units daily 9000 units daily    
gt170kg 0.6mg/kg/day 75 units/kg/day 75 units/kg/day    
Hospitalized antepartum patients may receive 5000 units UFH twice daily for prophylaxis to facilitate regional anesthesia
may be given in two divided doses
Adapted from ACOG Practice Bulletin 123, ACCP
Recommendations , RCOG Green Top Guideline 37a
23
Protocols for Therapeutic Dosing
LMWH Enoxaparin   Dalteparin   Tinzaparin Unfractionated heparin Warfarin (postpartum)
Dosing Antepartum or Postpartum 1mg/kg twice daily 200 units/kg/day 175 units/kg/day 10000 units or more twice daily adjusted to mid interval target aPTT (1.5-2.5) INR 2.0-3.0 (postpartum only)
Adapted from ACOG Practice Bulletin 123
24
Timing of Neuroaxial Anesthesia
Sources FDA Drug Safety Communication Nov,
2013 NYP protocol
25

• Post-Cesarean Prophylaxis
• Unfractionated heparin (UFH)
• The patient should receive the first dose of UFH
  on meeting criteria for PACU discharge, but no
  sooner than one hour after epidural catheter
  removal
• Standard order 5000 units SC every 12 hours
• If an epidural catheter remains in situ for pain
  control, it should not be removed until 3 hours
  after last dose of UFH
• Intraoperative UFH (infrequent) should be given
  no sooner than 30 minutes after spinal or epidural

NYP protocol
26

• Post-Cesarean Prophylaxis
• Low-molecular-weight heparin (LMWH)
• The patient should receive the first dose of LMWH
  no sooner than 6 hours postoperatively regardless
  of anesthesia technique
• If an epidural catheter remains in situ for pain
  control, it should not be removed until 12 hours
  after last dose of LMWH
• If the epidural catheter is to be removed prior
  to a dose of LMWH, the LMWH may not be given
  until 4 hours after removal

Sources FDA Drug Safety Communication Nov,
2013 NYP protocol
27

• Therapeutic Postpartum Prophylaxis
• For patients who have therapeutic LMWH postpartum
  anticoagulation planned
• LMWH should be deferred until at least 24 hours
  after spinal needle placement or epidural
  catheter removal
• Prophylactic UFH dosing should be considered
  during the 24 hours postpartum after regional
  anesthesia for these patients
• For patients with major risk factors for
  hemorrhage precluding therapeutic LMWH (recent
  postpartum hemorrhage, wound hematoma,
  coagulopathy) prophylactic UFH and/or SCDs should
  be considered

28

• Conclusion
• All patients require VTE risk assessment at
  multiple time points in pregnancy and postpartum
• All patients undergoing cesarean delivery require
  mechanical prophylaxis, early ambulation, and
  adequate hydration
• Women with additional risk factors for VTE after
  delivery will benefit from pharmacologic
  prophylaxis
• Empiric pharmacologic prophylaxis for all women
  undergoing cesarean delivery and for all
  antepartum hospital admissions is a reasonable
  clinical strategy